Administration, drugs subconjunctival injections

Topically applied drugs 221 Subconjunctival injections 223 Parenteral administration 224... 

Even in the inflamed eye, drug levels achieved in the anterior segment following parenteral administration alone using routine dosages are likely to be lower than those achieved by combined topical and subconjunctival administration. However, parenteral medication in combination with subconjunctival injection is necessary to achieve therapeutic levels of drug in the chorioretina. 

Davis et al. (49) investigated topical versus subconjunctival versus intramuscular (IM) tobramycin in a rabbit model of Pseudomonas keratitis. Topical application (two drops every 30 minutes) was found to be the most effective followed by subconjunctival and IM administrations. Neither local application had a significant effect on disease in the contralateral eye. Similar findings were reported by Leibowitz et al. (50) who showed that 16 hourly topical antibiotic drops were more effective than large single intravenous (TV) or subconjunctival injections. Ocular drug levels were not reported in either of these studies. Subconjunctival injections of ciprofloxacin have been studied in the rabbit (51). It was found that although potentially therapeutic levels were detected in the aqueous, vitreous levels were consistently low. 

Barza et al. (54) later reported that after subconjunctival injection of gentamicin, higher drug concentrations were found in ocular tissues from normal eyes than from inflamed, infected (Staphylococcus aureus endophthalmitis) eyes, despite the presumed reduction in blood-eye barrier in the inflamed eye. This result was not due to altered drainage into the tear film but may have been caused by increased ocular and orbital vascularity or decreased half-life within the eye (55). Similar results have been reported by Levine and Aronson (46) who found that inflammation caused a twofold decrease in ocular absorption of radiolabeled cortisol after retrobulbar injection although no such difference was seen following subconjunctival injection. Peak ocular concentrations were observed five minutes after administration. These authors also speculated that the difference in ocular absorption after retrobulbar injection was probably due to more rapid steroid removal from... 

Drugs were administered by means of topical instillation, subconjunctival injection or electrophoresis (current 0.5 mA, exposure 10 min). A combination of the above mechanisms was employed as well. Anterior chamber fluids were extracted by way of syringe with puncturing of the anterior chamber at hourly intervals following the administration of the drugs. Anson s biochemical method was used for assessing the proteolytic activity of anterior chamber fluid. 

In-depth discussions of the anatomy of the eye and adnexa have been adequately covered elsewhere in the pharmaceutical literature [13-17] and in recent texts on ocular anatomy. Here a brief overview is presented of the critical anatomical features that influence the nature and administration of ophthalmic preparations. In this discussion, consideration will be given primarily to drugs applied topically, that is, onto the cornea or conjunctiva or into the palpebral fornices. Increasingly, drugs are being developed for administration by parenteral-type dosage forms subconjunctivally, into the anterior and posterior chambers, the vitreous chamber, Tenon s capsule, or by retrobulbar injection. 

Very few injectable dosage forms have been specifically developed and approved by FDA for intraocular use. However, the ophthalmologist uses available parenteral dosage forms to deliver antiinfectives, corti-costerioids, and anesthetic products to achieve higher therapeutic concentrations intraocularly than can ordinarily be achieved by topical or systemic administration. These unapproved or off-label uses have developed over time as part of the physician s practice of medicine. However, these drugs are usually administered by subconjunctival or retrobulbar injection and rarely are they injected directly in the eye [301]. 

When higher concentrations of drugs, particularly corticosteroids and antibiotics, are required in the eye than can be delivered by topical administration, local injections into the periocular tissues can be considered. Periocnlar drug delivery includes subconjunctival, snb-Tenon s, retrobulbar, and peribulbar administration. 

Anterior sub-Tenon s injection offers no significant advantages over subconjunctival dmg administration. In fact, snb-Tenon s injection delivers lower qnantities of drug to the eye and is associated with a greater risk of perfttrating the globe. Despite these disadvantages, however, anterior snb-Tenon s injections of corticosteroids are occasionally nsed in the treatment of severe nveitis. 

Classical pharmacokinetic models of systemicaUy administered drugs (see Chapter 1) do not fuUy apply to many ophthalmic drugs. Most ophthalmic medications are formulated to be apphed topically or may be injected by subconjunctival, sub-Tenon s, and retrobulbar routes (Figure 63-1 and Table 63-1). Although similar principles of absorption, distribution, metabolism, and excretion determine drug disposition in the eye, these alternative routes of drug administration introduce other variables in compartmental analysis. 

Semi-solid bioerodible implant materials would enable the delivery of soft implants with a needle and syringe. Heller introduced such a material, poly(orthoester) IV, that shows long residence time after subconjunctival administration, an erosion-controlled drug release, and ocular biocompatibility. Depending on the ocular site of injection, the ocular lifetime of the drug ranges from 5 to 6 months. 

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